PROJECT SUMMARY / ABSTRACT Pulmonary arterial hypertension (PAH) is a progressive and incurable condition, with a median survival of less than 10 years. Right ventricle (RV) adaptation to increased pulmonary artery (PA) pressures is a crucial factor in determining disease outcomes. However, metrics of RV function remain absent from many clinical risk scores, highlighting a need to determine the best way to measure RV function. By measuring the ratio of RV contractility to afterload, RV-PA coupling represents a metric which can quantify the RV adaptive response. RV-PA coupling has demonstrated utility as a high-fidelity predictor of clinical outcomes but is not routinely measured in clinical practice due to its resource-intensive nature. Thus, there is an urgent need to identify accessible metrics that can serve as surrogates for RV-PA coupling and report on RV adaptation. In this proposed work, we hypothesize that a set of clinically available metrics can be identified as surrogates for RV-PA coupling and can improve survival predictions of existing clinical risk scores. We have access to data from over 100 subjects followed for up to 10 years who underwent same-day right heart catheterization (RHC), RV pressure-volume (PV) loop analysis, cardiac MRI (CMR), and transthoracic echocardiogram (TTE) at a single center after referral for suspected PAH. Leveraging this unique dataset, our proposed research aims to 1) identify a set of clinically available metrics using a multivariable model which can act as surrogates for RV-PA coupling and indicators of RV adaptation. We will 2) evaluate the association between the metrics from this model and transplant-free survival in our single-center cohort. We will then 3) externally validate survival predictions in a multi-center cohort and determine if these metrics improve prognostic value when added into the widely used clinical risk score, the REVEAL Lite 2.0. In conclusion, the proposed study aims to demonstrate that clinically accessible metrics can serve as surrogates for RV-PA coupling and indicators of RV adaptation. In identifying these metrics, this work has the potential to improve survival predictions and our assessment of disease progression in PAH. This research will provide valuable research skills in clinical study design, prediction model development, and longitudinal analysis. The proposed work will serve as an exceptional opportunity for developing the fundamental skills and generating the preliminary data for a future K-level Career Development Award.